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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Related Experiment Video

Updated: May 17, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

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Tumour interstitial fluid-enriched phosphoethanolamine suppresses T cell function.

Yupeng Wang¹, Drew Wilfahrt^2,3, Patrick Jonker⁴

¹Tsinghua Medical School, Beijing, China.

Nature Cell Biology

|April 21, 2025

Summary

This summary is machine-generated.

Tumor nutrient stress impairs anti-tumor immunity. Researchers found phosphoethanolamine (pEtn) in tumor fluid hinders T cell function by disrupting signaling, highlighting pEtn as a target for improving cancer immunity.

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Last Updated: May 17, 2025

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Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

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Published on: June 7, 2018

Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model

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Published on: April 13, 2015

Area of Science:

Immunology
Cancer Biology
Metabolomics

Background:

Nutrient stress in the tumor microenvironment is a significant barrier to anti-tumor immunity.
Tumor interstitial fluid contains metabolites that can suppress immune cell function.
Isolating the impact of nutrient stress from other suppressive factors is challenging.

Purpose of the Study:

To investigate the isolated effect of tumor nutrient stress on CD8+ T cell function.
To identify specific metabolites responsible for T cell dysfunction in the tumor microenvironment.
To evaluate the therapeutic potential of targeting identified metabolites for enhancing anti-tumor immunity.

Main Methods:

Developed a chemically defined medium (TIFM) mimicking tumor interstitial fluid metabolomics.
Cultured CD8+ T cells in TIFM to assess expansion and effector functions.
Identified phosphoethanolamine (pEtn) as a key metabolite driving T cell dysfunction.
Analyzed the mechanism of pEtn-mediated T cell suppression, focusing on T cell receptor signaling and diacylglycerol depletion.
Assessed the impact of reducing pEtn accumulation on intratumoral T cell function and tumor control in vivo.

Main Results:

Culture of CD8+ T cells in TIFM led to limited expansion and impaired effector functions.
Phosphoethanolamine (pEtn) was identified as a primary driver of T cell dysfunction.
pEtn suppressed T cell receptor signaling by depleting diacylglycerol, essential for signal transduction.
Reducing pEtn accumulation in tumors enhanced intratumoral T cell function and improved tumor control.

Conclusions:

Tumor nutrient stress alone is sufficient to induce T cell dysfunction.
Phosphoethanolamine (pEtn) accumulation in tumors plays a dominant role in immunosuppression.
Targeting pEtn accumulation represents a promising strategy to enhance anti-tumor immunity and improve cancer treatment outcomes.